The overall goal of this Program Project Grant is to elucidate basic mechanisms that are responsible for regulation of the cerebral circulation. The focus of the research is on cerebral circulation, cerebral endothelium and the blood-brain barrier, and the choroid plexus. The program can be characterized by four themes: First, responses of cerebral blood vessels to neurohumoral stimuli will be examined. Studies are proposed to examine effects of peripheral and central neural pathways on cerebral blood flow, and to study responses to vasoactive amines and hormones in vitro and in vivo. Second, mediators of injury and mechanisms of protection will be examined. Effects of eicosanoids will be studied in vitro and in vivo, in cerebral vessels and in choroid plexus. Studies also are proposed to examine the role of medium-chain fatty acids, oxygen radicals, and inflammatory mediators on cerebral endothelium and blood vessels. Third, induction of properties of cerebral blood vessels will be studied. Experiments are proposed to examine induction of barrier-properties in endothelium by astrocytes and induction of cerebral vascular hypertrophy by sympathetic nerves. Fourth, cerebral vascular effects of chronic hypertension will be studied. Experiments are proposed to examine hemodynamic consequences of vascular hypertrophy, intrinsic abnormalities of the blood-brain barrier in chronic hypertension, and mechanism by which K+ protects cerebral vessels. The program consists of five research projects: Studies of the Blood-Brain Barrier In Vitro, Leukotrienes and Medium-Chain Fatty Acids in the Central Nervous System, Central Neural Regulation of Cerebral Blood Flow, Neurohumoral Regulation of Cerebral Circulation, and Effects of Hypertension on Cerebral Circulation. These projects are supported by 3 core facilities: Administrative/Biostatistics, Morphology, and Hypertensive Animal Core.